EXCEED THE SPACE PROVIDED. The study of acquired and inherited human diseases has provided new insights into the role of ion channel mutations in a wide variety of human diseases (ion channelopathies). Although defects in anion (chloride) channels have been definitively linked to human diseases such as cystic fibrosis, generalized myotonias, and Batter Syndrome, the possible role of ion channelopathies in cardiovascular disease has been mostly limited to the consideration of cation channel defects, and the role of anion channels in many types of cardiovascular disease has not yet been systematically investigated. A major objective of this Center of Biomedical Research Excellence (COBRE) is to advance our present understanding of the molecular and biophysical properties of anion channels and their regulation in the cardiovascular'system, and determine their role in cardiovascular disease, using complementary experimental approaches that include well-defined animal disease models, transgenic mice, molecular biology and genetics, electrophysiology, biomedical imaging and functional genomics and proteomics. This competitive continuation application for COBRE program support represents a comprehensive, multidisciplinary effort involving the coordination and integration of five separate, but closely related, research projects, supported by three core facilities and an administrative/ mentoring core. This COBRE program offers a variety of unique opportunities: (1) to advance knowledge regarding the role of anion channelopathies in cardiovascular disease, (2) to support and promote the development of a cadre of young, competitive biomedical research investigators at the University of Nevada, (3) to promote the development of new, state-of-the-art transgenic, genomic, proteomic and molecular genetic resources at the University of Nevada School of Medicine (UNSOM). The long term objective of this NCRR-supported Center is to eventually transition this program into a Cardiovascular Research Center at UNSOM supported by a NHLBI Program Project Grant.